Tissue distribution and metabolism of drugs. IV. Accumulation and penetration of some antibiotics in rat lungs.

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The lung accumulation and permeation of some antibiotics were studied using an isolated blood-perfused rat lung preparation with artificial ventilation and the intact lung of anesthetized rats in vivo. Leucomycin A3 and erythromycin, which have been widely used for the treatment of pulmonary infections, were accumulated well in the lung, while tetracycline and chloramphenicol did not show specific accumulation. The specific accumulation of leucomycin A3 and erythromycin is probably due to the fact that both drugs have an amino group and a strongly lipophilic group. In the case of intratracheal administration in the perfused lung, the transport of these antibiotics from alveoli to the blood was shown to be dependent on their lipid solubility, and the drug distribution in the lung was found to be similar to that from the perfusate in the equilibrium state. However, in the in vivo distribution study, marked accumulation of erythromycin after intratracheal administration was observed as compared with intravenous administration, whereas, the distribution of leucomycin A3 was not greatly affected by the route of administration. On the basis of these experimental findings, drug delivery systems are discussed in relation to the effective distribution of drugs in the lung.

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